This application details the experience, qualifications and short- and long-term plans for the patient-oriented research and mentoring activities of Randall F. Holcombe, MD, Chief of Hematology/Oncology at the University of California, Irvine and Associate Director for Clinical Research of the Chao Family Comprehensive Cancer Center. Since completion of Hematology/Oncology sub-specialty training in 1989, Dr. Holcombe has established an academic career in clinical and translational patient-oriented research involving both clinical and basic investigations in the areas of oncology, immunology and genetics. He has been successful in conducting clinical/translational trials and in obtaining extramural support for these activities. Currently and over the past several years, he has also been active in mentoring beginning clinical investigators. This application for the Midcareer Investigator Award in Patient-Oriented Research will provide support to allow Dr. Holcombe to continue and expand upon these activities. This application will outline proposed research and mentoring activities, institutional support for these activities, and documentation of Dr. Holcombe's commitment to a career in patient-oriented research. This is a second revision of a Midcareer Investigator Award in Patient-Oriented Research (K24) initially submitted 10/1/98, with a first revision submitted 7/1/99. Substantial modifications in response to questions raised in the first summary statement were included in the first revision. While minimal criticisms of the proposal were noted in the second summary statement, additional information that further strengthens the application has been provided in preparation of this second revision.